Detection of salivary gland and sinonasal fusions by a next‐generation sequencing based, ligation‐dependent, multiplex RT‐PCR assay

Author:

Lanic Marie‐Delphine1,Guérin René2,Wassef Michel3,Durdilly Pauline2,Rainville Vinciane1,Sater Vincent2,Jardin Fabrice1,Ruminy Philippe1,Costes‐Martineau Valérie4,Laé Marick12ORCID

Affiliation:

1. INSERM U1245, Cancer Center Henri Becquerel, Institute of Research and Innovation in Biomedicine (IRIB), University of Normandy, UNIROUEN Rouen France

2. Department of Pathology Centre Henri Becquerel Rouen France

3. Department of Pathology Hôpital Lariboisière Paris France

4. Department of Pathology CHU de Montpellier Montpellier France

Abstract

AimsThe discovery of tumour type‐specific gene fusion oncogenes in benign and malignant salivary gland and sinonasal (SGSN) tumours has significantly increased our knowledge about their molecular pathology and classification.Methods and resultsWe developed a new targeted multiplexed next‐generation sequencing (NGS)‐based method that utilizes ligation dependent reverse‐transcriptase polymerase chain reaction (LD‐RT‐PCR) to detect oncogenic fusion transcripts involving 116 genes, leading to 96 gene fusions known to be recurrently rearranged in these tumours. In all, 180 SGSN tumours (formalin‐fixed, paraffin‐embedded samples, 141 specimens and 39 core needle biopsies) from the REFCORpath (French network for rare head and neck cancers) with previously identified fusion genes by fluorescent in situ hybridisation (FISH), RT‐PCR, or molecular immunohistochemistry were selected to test its specificity and sensitivity and validate its diagnostic use. Tested tumours encompassed 14 major tumours types, including secretory carcinoma, mucoepidermoid carcinoma, adenoid cystic carcinoma, salivary gland intraductal carcinoma, clear cell carcinoma, pleomorphic adenoma, adamantinoma‐like Ewing Sarcoma, EWSR1::COLCA2 sinonasal sarcoma, DEK::AFF2 sinonasal carcinoma, and biphenotypic sinonasal sarcoma. In‐frame fusion transcripts were detected in 97.8% of cases (176/180). Gene fusion assay results correlated with conventional techniques (immunohistochemistry [IHC], FISH, and RT‐PCR) in 176/180 tumours (97.8%).ConclusionThis targeted multiplexed NGS‐based LD‐RT‐PCR method is a robust, highly sensitive method for the detection of recurrent gene fusions from routine clinical SGSN tumours. It can be easily customized to cover new fusions. These results are promising for implementing an integrated NGS system to rapidly detect genetic aberrations, facilitating accurate, genomics‐based diagnoses, and accelerate time to precision therapies in SGSN tumours.

Publisher

Wiley

Subject

General Medicine,Histology,Pathology and Forensic Medicine

Reference100 articles.

1. Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer.MitelmanF JohanssonBandMertensFeds.https://mitelmandatabase.isb‐cgc.org;2022.

2. The emerging complexity of gene fusions in cancer

3. Diagnostic and therapeutic implications of new molecular biomarkers in salivary gland cancers

4. The Role of Molecular Testing in the Differential Diagnosis of Salivary Gland Carcinomas

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